A Randomized, Open-Label, Phase 3 Trial of Tisotumab Vedotin vs Investigator*s Choice Chemotherapy in Second- or Third-Line Recurrent or Metastatic Cervical Cancer

1.Age >=18 years , or considered an adult by local regulations, at time of
consent.

Has recurrent or metastatic cervical cancer with squamous cell, adenocarcinoma,
or adenosquamous histology and:

Has experienced disease progression during or after treatment with a standard
of care systemic chemotherapy doublet, or platinum-based therapy (if eligible),
defined as either:
paclitaxel+cisplatin+bevacizumab, or + anti-PD-(L)1 agent
paclitaxel+carboplatin+bevacizumab, or + anti-PD-(L)1 agent
paclitaxel+topotecan/nogitecan+bevacizumab + anti-PD-(L)1 agent

2. Has ECOG performance status of 0 or 1 prior to randomization.

3. Has life expectancy of at least 3 months.

4. Has a negative serum pregnancy test for participants of reproductive
potential. Participants that are postmenopausal, permanently sterilized or
previously subjected to bilateral oophorectomy, bilateral salpingectomy and/or
hysterectomy can be considered as not having reproductive potential (refer to
Section 10.4 of protocol).

5. Participants of reproductive potential must agree to use adequate
contraception during and for 6 months after the last study treatment
administration. Adequate contraception is defined as highly effective methods
of contraception (refer to Section 10.4 of protocol). Two highly effective
methods of contraception must be used in countries where this is required.

6. Must agree not to breastfeed or donate ova, starting at the time of informed
consent and continuing through 6 months after receiving the last dose of study
drug administration

7. Where required by local health authorities, has negative serology for
hepatitis B surface antigen (HBsAg)/HBV DNA, or hepatitis C antibody (HCVAb) or
RNA. Active hepatitis C is defined by a known positive HCVAb result and known
quantitative HCV RNA results greater than the lower limits of detection of the
assay.

8. Must be able to provide tumor tissue. The most recent archival tumor biopsy
is preferred if collected within the last 2 years. If an archival tumor biopsy
less than 2 years old is not available, a fresh tumor biopsy will be collected
before initiation of study treatment, if clinically feasible. If a fresh biopsy
cannot be collected, the most recent archival tumor sample may be submitted,
even if obtained more than 2 years prior to participant enrollment.

9. Must be willing and able to adhere to the prohibitions and restrictions
specified in this protocol.

10. Measurable disease according to RECIST v1.1 as assessed by the investigator

11. Must demonstrate acceptable screening laboratory values (please refer to
protocol pg. 32)

1. Has primary neuroendocrine, lymphoid, sarcomatoid, or other histologies not
mentioned in inclusion criterion 3 (refer to Section 5.1 of protocol).

2. Has clinically significant bleeding issues or risks:
- Known past or current coagulation defects leading to an increased risk of
bleeding
- Diffuse alveolar hemorrhage from vasculitis
- Known bleeding diathesis
- Ongoing major bleeding (i.e. participant requires a transfusion of >2
platelet concentrates within 14 days of the first dose of the study treatment)
- Trauma with increased risk of life-threatening bleeding
- History of severe head trauma or intracranial surgery within 8 weeks of study
entry.

3. Has cardiovascular issues or risks:
- Clinically significant cardiac disease, including unstable angina or acute
myocardial infarction, 6 months prior to screening
- Any medical history of congestive heart failure (grade III or IV as
classified by the New York Heart Association)
- Any medical history of decreased ejection fraction of <45%
- A marked baseline prolongation of QT/QTc interval (e.g., repeated
demonstration of a QTc interval >450 msec)
- A complete left bundle branch block (defined as QRS interval >=120 msec in
left bundle branch block form) or an incomplete left bundle branch block

4. Central nervous system (CNS): any history of intracerebral arteriovenous
malformation, cerebral aneurysm, or stroke (transient ischemic attack >1 month
prior to screening is allowed).

5. Ophthalmological conditions: Active ocular surface disease or a history of
cicatricial conjunctivitis or inflammatory conditions that predispose to
cicatrizing conjunctivitis (e.g. Wagner syndrome, atopic keratoconjunctivitis,
autoimmune disease affecting the eyes), ocular Stevens-Johnson syndrome or
toxic epidermal necrolysis, mucus pemphigoid, and participants with penetrating
ocular transplants are ineligible. Cataracts alone is not an exclusion
criterion.

6. Other cancer: known past or current malignancy other than inclusion
diagnosis. Exceptions are malignancies with a negligible risk of metastasis or
death (e.g., 5year OS =90%) such as non-invasive basal cell or squamous cell
skin carcinoma; non-invasive, superficial bladder cancer, and ductal carcinoma
in situ.

7. Brain metastases are allowed if the following criteria are met: definitive
therapy (eg, surgery or stereotactic brain radiotherapy) has been completed >8
weeks before the first dose of study treatment; no evidence of clinical or
radiologic progression of the brain metastases; participant has completed
perioperative corticosteroid therapy or steroid taper. NOTE: Chronic steroid
therapy is acceptable provided that the dose is stable for 1 month prior to
screening.

8. Surgery/Procedures: major surgery within 4 weeks or minor surgery within 7
days prior to the first study treatment administration.

9. Peripheral neuropathy grade > 2

10. Prior anti-cancer therapy:
- Any prior treatment with MMAE-derived drug.
- Radiotherapy within 21 days prior to the first administration of study
treatment. Participants must have recovered from all clinically significant
radiation-related toxicities. At least 42 days must have elapsed from the last
administration of chemo radiotherapy.
- Small molecules, chemotherapy, immunotherapy, or monoclonal antibodies within
28 days prior to the first administration of study treatment.
- Currently participating in or has participated in a study of an
investigational agent or device and received active treatment within 28 days
prior to the first dose of study treatment.

11. Has known seropositivity of human immunodeficiency virus (HIV); known
medical history of hepatitis B or C infection. Note: No testing for HIV,
hepatitis B, or hepatitis C is required, unless mandated by local health
authorities. Exceptions include latent or controlled HIV infection.

12. Has a diagnosis of immunodeficiency or is receiving systemic steroid
therapy (dose exceeding 10 mg daily of prednisone or equivalent) or any other
form of immunosuppressive therapy within 7 days prior to the first dose of
tisotumab vedotin

13. Is pregnant or intends to conceive children within 6 months of ending study
treatment

14. Known allergies, hypersensitivity, or intolerance to study treatment or its
excipients (refer to the Investigator*s Brochure for further information on
tisotumab vedotin)